The amino acid, arginine is converted to nitric oxide and citrulline by a family of enzymes, collectively known as "nitric oxide synthase". The free radical, nitric oxide, has a number of diverse functions depending on the locality and type of cell involved in its production. These include cell mediated immunity, regulation of blood pressure, and neurotransmission via stimulation of guanylate cyclase. Inhibition of the enzyme has, among other effects, been linked to increased arterial blood pressure. Several inhibitors have been synthesized in the past few years; virtually all are arginine derivatives with modified guanidine groups. A similar modification with radionuclide substitution would allow for in vivo imaging of the enzyme and functional studies. A) N(G)-METHYLARGININE: One of the most widely studied NOS inhibitors is N(G)-methylarginine (NMA). Conceptually, replacing the N-methyl with a positron emitting carbon-11 N-methyl would give an easily available imaging agent. Due to its short half-life, conventional methods of obtaining this compound, with C-11 substitution are infeasable. A number of studies were undertaken to directly introduce a methyl group to the guanidine residue of arginine or protected arginines. All approaches thus far, resulted in no incorporation or in total destruction of the arginine skeleton. B) FLUORINATED ARGININES: Current studies involve synthesis of N(G)- alkyl-fluoro derivatives. The fluoride introduction is envisaged to be quite facile by hydrofluorination of multiple bonds or nucleophilic displacement at saturated carbon. Cold compounds are synthesized by methods analogous to recently published procedures. Bioassay studies will follow.